Determining population-level allocation strategies for COVID-19 treatments in the United States using a quantitative framework, a case study using nirmatrelvir/ritonavir (preprint)

BackgroundNew COVID-19 medications force decision makers to weigh limited evidence of efficacy and cost in determining which patient populations to target for treatment. A case in point is nirmatrelvir/ritonavir, a drug that has been recommended for elderly, high-risk individuals, regardless of vaccination status, even though clinical trials have only evaluated it in unvaccinated patients. A simple optimization framework might inform a more reasoned approach to the tradeoffs implicit in the treatment allocation decision. MethodsWe used a mathematical model to analyze the cost-effectiveness of four nirmatrelvir/ritonavir allocation strategies, stratified by vaccination status and risk for severe disease. We considered treatment effectiveness at preventing hospitalization ranging from 21% to 89%. Sensitivity analyses were performed on major parameters of interest. A web-based tool was developed to permit decision-makers to tailor the analysis to their settings and priorities. ResultsProviding nirmatrelvir/ritonavir to unvaccinated patients at high-risk for severe disease was cost-saving when effectiveness against hospitalization exceeded 33% and cost-effective under all other data scenarios we considered. The cost-effectiveness of other allocation strategies, including those for vaccinated adults and those at lower-risk for severe disease, depended on willingness-to-pay thresholds, treatment cost and effectiveness, and the likelihood of severe disease. ConclusionsPriority for nirmatrelvir/ritonavir treatment should be given to unvaccinated persons at high-risk of severe disease from COVID-19. Further priority may be assigned by weighing treatment effectiveness, disease severity, drug cost, and willingness to pay for deaths averted.

Access to COVID-19 Vaccines in High-, Middle-, and Low-Income Countries Hosting Clinical Trials (preprint)

The COVID-19 pandemic has led to the rapid development of multiple vaccines, vaccines that were tested in clinical trials located in several countries around the world. Because prior research has shown that pharmaceuticals do not receive consistent and timely authorization for use in lower-income countries where they are tested, we conducted a cross-sectional study examining the authorization or approval and delivery for COVID-19 vaccines recommended by the World Health Organization (WHO) in the countries where they were tested. While countries of varying incomes have largely authorized the COVID-19 vaccines tested within their populations for use, high-income countries have received proportionately more doses, enabling them to more fully vaccinate their populations. As many lower-income countries continue to experience inequitable shortfalls in COVID-19 vaccine supply amid the ongoing pandemic, efforts must be undertaken to ensure timely access in countries across all income groups, including those hosting clinical trials.

Evaluation of the Anticipated Burden of COVID-19 on Hospital-Based Healthcare Services Across the United States (preprint)

Background: Coronavirus disease-19 (COVID-19) is a global pandemic, with the potential to infect nearly 60% of the population. The anticipated spread of the virus requires an urgent appraisal of the capacity of US healthcare services and the identification of states most vulnerable to exceeding their capacity Methods: In the American Hospital Association survey for 2018, a database of US community hospitals, we identified total inpatient beds, adult intensive care unit (ICU) beds, and airborne isolation rooms across all hospitals in each state of continental US. The burden of COVID-19 hospitalizations was estimated based on a median hospitalization duration of 12 days and was evaluated for a 30-day reporting period. Results: At 5155 US community hospitals across 48 states in the contiguous US and Washington DC, there were a total of 788,032 inpatient beds, 68,280 adult ICU beds, and 44,222 isolation rooms. The median daily bed occupancy was 62.8% (IQR 58.1%, 66.6%) across states. Nationally, for every 10,000 individuals, there are 24.2 inpatient beds, 2.8 adult ICU beds, and 1.4 isolation beds. There is a 3-fold variation in the number of inpatient beds available across the US, ranging from 16.4 per 10,000 in Oregon to 47 per 10,000 in South Dakota. There was also a similar 3-fold variation in available or non-occupied beds, ranging from 4.7 per 10,000 in Connecticut through 18.3 per 10,000 in North Dakota. The availability of ICU beds is low nationally, ranging from 1.4 per 10,000 in Nevada to 4.7 per 10000 in Washington DC. Hospitalizations for COVID-19 in a median 0.2% (IQR 0.2 %, 0.3%) of state population, or 1.4% of state's older adults (1.0%, 1.9%) will require all non-occupied beds. Further, a median 0.6% (0.5%, 0.8%) of state population, or 3.9% (3.1%, 4.6%) of older individuals would require 100% of inpatient beds. Conclusion: The COVID-19 pandemic is likely to overwhelm the limited number of inpatient and ICU beds for the US population. Hospitals in half of US states would exceed capacity if less than 0.2% of the state population requires hospitalization in any given month.